Abstract
The author describes investigations on ABO and Lewis blood-group antigens from the time in the 1940s when practically nothing was known about their chemical structure until today when the genes ultimately responsible for the appearance of the antigens on the red blood cell surface have been defined in molecular terms. The early work was carried out on glycoproteins in secretions that have the same serological specificity as the A, B, H, and Lewis antigens on red cells. Indirect methods of inhibition of haemagglutination with simple sugars and inhibition of degradation with exo-glycosidases led to the identification of the immunodominant sugars in the determinant structures. The sequential degradation with exo-glycosidases established the precursor-product relationship of A and B to H and showed that a single sugar masked the underlying specific H structure. Fragmentation of the purified glycoproteins with mild acid or alkali led eventually to defined structures for the five specificities A, B, H, Le(a) and Le(b). Knowledge of the chemical basis of the blood-group reactions enabled schemes to be proposed for the genetic control and biosynthesis of the glycoproteins that explained the interactions at the phenotypic level between the ABO, H, Secretor and Lewis genes. The proposal that the primary protein products of the blood-group genes are glycosyltransferase enzymes that transfer the immunodominant sugar to complete the determinant structures was confirmed and the characterization of these glycosyltransferases has enabled the blood-group genes to be cloned and sequenced by others. Studies on the P1 determinant in the blood-group P system and the Sd(a) determinant in the Sid system were also performed on soluble sources of material that carried the same specificity as the antigens on the red cell surface. A glycoprotein isolated from sheep hydatid cyst fluid yielded the structure of the P1 determinant and the structure of the Sd(a) determinant was identified amongst fragments released from Tamm-Horsfall glycoprotein which is secreted in soluble form in human urine.
